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Background <p>Cerebral small vessel disease (CSVD) often coexists with neurodegenerative pathologies, yet their role remains underexplored. This study aims to determine their prevalence, risk factors, and cognitive effects in patients with deep perforator arteriopathy (DPA) or cerebral amyloid angiopathy (CAA) using the biomarker-based ATN classification.</p> Methods <p>In this cross-sectional study 186 patients (median age 75 years, 41% females, 111 with probable CAA, 75 with DPA) underwent MRI for analysis of CSVD severity and etiology, and lumbar puncture for analysis of cerebrospinal fluid amyloid-β 42/40 ratio, phosphorylated-tau, total-tau and neurofilament light. ATN profiles were related to clinical characteristics, MRI markers and cognitive performance in multivariate regression models.</p> Results <p>Among CSVD patients, 30% had normal biomarkers (A-T-N-), 33% were within the AD pathology continuum (A + T ± N ± : 47% in CAA vs. 13% in DPA, p &lt; .001), and 37% showed non-AD pathological changes (A-T ± N + : 53% in DPA vs. 25% in CAA, p &lt; .001). The AD pathology continuum was associated with a severe lobar hemorrhagic phenotype and cognitive impairment, while non-AD pathological change was related to CSVD severity, history of stroke and similarly cognitive impairment. Both pathological ATN profiles were further related to lower MMSE scores (A + T ± N ± : B = − 3.3, p = .006; A-T ± N + :&#xa0;B = − 2.7, p = .021).</p> Conclusions <p>Using biomarkers, this study confirms in vivo&#xa0;that CSVD frequently co-occurs with neurodegenerative pathologies, exerting detrimental effects on cognitive health.</p>

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Risk factors and clinical significance of neurodegenerative co-pathologies in symptomatic cerebral small vessel disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月18日

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  • Philipp Arndt,
  • Malte Pfister,
  • Valentina Perosa,
  • Hendrik Mattern,
  • Jose Bernal,
  • Anna-Charlotte John,
  • Marc Dörner,
  • Patrick Müller,
  • Rüdiger C. Braun-Dullaeus,
  • Cornelia Garz,
  • Christopher Nelke,
  • Alma Kokott,
  • Robin Jansen,
  • Michael Gliem,
  • Sven G. Meuth,
  • Solveig Henneicke,
  • Stefan Vielhaber,
  • Katja Neumann,
  • Stefanie Schreiber

摘要

Background

Cerebral small vessel disease (CSVD) often coexists with neurodegenerative pathologies, yet their role remains underexplored. This study aims to determine their prevalence, risk factors, and cognitive effects in patients with deep perforator arteriopathy (DPA) or cerebral amyloid angiopathy (CAA) using the biomarker-based ATN classification.

Methods

In this cross-sectional study 186 patients (median age 75 years, 41% females, 111 with probable CAA, 75 with DPA) underwent MRI for analysis of CSVD severity and etiology, and lumbar puncture for analysis of cerebrospinal fluid amyloid-β 42/40 ratio, phosphorylated-tau, total-tau and neurofilament light. ATN profiles were related to clinical characteristics, MRI markers and cognitive performance in multivariate regression models.

Results

Among CSVD patients, 30% had normal biomarkers (A-T-N-), 33% were within the AD pathology continuum (A + T ± N ± : 47% in CAA vs. 13% in DPA, p < .001), and 37% showed non-AD pathological changes (A-T ± N + : 53% in DPA vs. 25% in CAA, p < .001). The AD pathology continuum was associated with a severe lobar hemorrhagic phenotype and cognitive impairment, while non-AD pathological change was related to CSVD severity, history of stroke and similarly cognitive impairment. Both pathological ATN profiles were further related to lower MMSE scores (A + T ± N ± : B = − 3.3, p = .006; A-T ± N + : B = − 2.7, p = .021).

Conclusions

Using biomarkers, this study confirms in vivo that CSVD frequently co-occurs with neurodegenerative pathologies, exerting detrimental effects on cognitive health.